Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cardiovascular response to 5-hydroxytryptamine (5-HT) challenge has been previously described in cattle. Abrupt bradycardia, followed by tachycardia, triphasic systemic blood pressure response, and pulmonary hypertension were the major changes elicited by 5-HT. The purpose of the present study was to determine whether the cardiovascular response to 5-HT in calves was attributable to 5-HT2 receptors. A specific 5-HT2 antagonist (metrenperone, 0.05 mg/kg) was administered intramuscular to six unsedated Friesian calves 30 min before the animals were given a 5-min intravenous 5-HT infusion. Mean systemic arterial (SAP), mean pulmonary arterial (PAP), pulmonary capillary wedge (PW) pressures were obtained by means of fluid-filled catheters, and cardiac output (CO) was measured by the thermodilution technique. Heart rate, stroke volume, systemic (SVR) and pulmonary (PVR) vascular resistances were calculated. Administration of 5-HT after metrenperone induced a short-lasting period of severe bradycardia followed by tachycardia and increased CO. The systemic blood pressure response was exclusively hypotensive and associated with a decrease in SVR. Conversely, PAP, PW, and PVR were not modified by 5-HT administration. The results establish that 5-HT induced systemic as well as pulmonary hypertension is mediated through the activation of type-2 serotonergic or alpha-adrenergic receptors, or both. In contrast, neither apnoea, bradycardia and hypotension, nor the positive chronotropic effect induced by 5-HT in cattle are mediated through such receptors.
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PMID:Cardiovascular response to intravenous administration of 5-hydroxytryptamine after type-2 receptor blockade, by metrenperone, in healthy calves. 1003 Jan 26

Influences of endothelium on contraction of aortic smooth muscle by various agents were studied and those in the preparations from Wistar Kyoto rat (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP) were compared. Endothelium depressed the contractions induced by noradrenaline and 5-hydroxytryptamine (5-HT). The time course of the contraction was bi- or tri-phasic in the former and slow rising monophasic in the latter. On the other hand, the depression was weaker in the contraction by prostaglandin F2alpha- and high K+. The depression was blocked by the removal of endothelium or in the presence of Nomega-nitro-L-arginine (L-NNA), indicating that nitric oxide (NO) released from endothelium was responsible for the inhibition. The inhibition was weaker in the preparation from SHRSP when compared to that in the preparation from WKY. Relaxation by acetylcholine (ACh) of the preparation precontracted in the presence of respective contractile agent was impaired in the preparation from SHRSP. It is concluded that mode of inhibition of the contraction varies depending on the agents used to initiate the contraction, i.e. depending on the mode of the release of NO. In the preparation from SHRSP, the influence of endothelium is impaired due to the reduced release of NO.
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PMID:Influences of endothelium on the time course of noradrenaline-, 5-HT-, prostaglandin F2alpha- and high-K+-induced contractions in aortae of WKY and SHRSP. 1037 29

Isatin (indole-2,3-dione) has been found in mammalian tissues as one of major components of tribulin, a postulated endogenous marker of stress and anxiety. I previously identified isatin as an endogenous inhibitor of monoamine oxidase (MAO) in the human urine and the brain of stroke-prone spontaneously hypertensive rats (SHRSP) using GC-MS. A single dose of isatin significantly increased norepinephrine (NE) and 5-hydroxytryptamine (5-HT) concentrations measured 2 h later in the various brain regions of normotensive Wistar Kyoto rats (WKY). Striatal acetylcholine (ACh) and dopamine (DA) levels significantly increased 2 h after the administration of isatin. Perfused through a microdialysis probe, isatin also produced a significant and concentration-dependent increase in the ACh and DA concentration in the perfusate from the rat striatum. In the patients with Parkinson's disease, urinary isatin concentrations tended to increase according to the severity of disease, as classified by the Hoehn and Yahr criteria. Isatin significantly increased striatal DA levels in a rat model of Parkinson's disease. Isatin may play a role in the regulation of the brain levels of ACh and DA. Furthermore, isatin has a wide spectrum of biological properties: (a) a marker of stress and anxiety, (b) an inhibitor of a number of enzymes, (c) an anti-seizure agent, (d) an inhibitor of benzodiazepin receptors and ANP binding to its receptors.
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PMID:[Pharmacological role of isatin, an endogenous MAO inhibitor]. 1077 57

Late-life depression is a serious health problem that is challenging to manage but generally responds well to pharmacotherapy. Selective serotonin (5-hydroxytryptamine: 5-HT) reuptake inhibitors (SSRIs), the most commonly prescribed antidepressants, are usually used as first-line agents for elderly patients with depression. Like most drugs, SSRIs have not been widely tested in clinical trials that approximate 'real-life' geriatric situations. However, studies completed to date provide valuable information about the efficacy, safety and tolerability of this class of antidepressants among older patients with depression, including those with depression secondary to stroke or dementia and those with other comorbid physical disorders. Although one SSRI may be more efficacious or better tolerated by elderly patients than another, existing data do not support such claims. However, other distinguishing features may influence the choice of agent. For example, fluoxetine, fluvoxamine and paroxetine are more likely to be involved in significant drug-drug interactions than are citalopram or sertraline. In contrast to the other SSRIs, fluoxetine has a half-life well in excess of 1 day, which can be an advantage when weaning the patient off therapy in that it may reduce the incidence of discontinuation symptoms, but a significant disadvantage if the patient cannot tolerate the drug or experiences an adverse drug-drug interaction.
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PMID:Selective serotonin reuptake inhibitors for late-life depression: a comparative review. 1139 44

Milnacipran is one of the first modern antidepressant drugs to be introduced into Japan, and the first dual-action antidepressant. Placebo-controlled clinical trials with this drug have demonstrated similar efficacy and superior tolerability to imipramine and mianserin. The good safety profile of the drug has been confirmed from open-label phase IV studies. There are indications, both from the randomized clinical trials and from the phase IV programme, that milnacipran may have a comparatively rapid onset of action, showing clear signs of efficacy after one week of treatment. This observation, which needs to be confirmed in an appropriately designed study, may be the clinical correlate of the rapid desensitization of 5-hydroxytryptamine (HT)1A receptors produced by milnacipran. A series of pilot studies have demonstrated the role of milnacipran in the management of certain affective disorders not adequately treated by classical antidepressants. These include bipolar disorder, treatment-resistant depression in the elderly and post-stroke depression. These findings merit confirmation in controlled studies, and open the way to using milnacipran to provide satisfactory treatment of these condi-
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PMID:Japanese experience with dual-action antidepressants. 1236 9

Anorectic drugs are widely used for the treatment of obesity. They are thought to decrease appetite through their effects on catecholamine or 5-hydroxytryptamine (5-HT) levels in the brain. Their use has been associated with epidemics of pulmonary hypertension and the development of valvular heart disease, hypertension, stroke and digital or mesenteric ischemia. Understanding the mechanism of the cardiovascular toxicity of anorectic drugs is important because of the modern epidemic of obesity and the resulting plethora of new anorexigens, many of which share similar mechanisms with those that have previously caused cardiovascular disease. In addition, the mechanism by which anorexigens cause vascular disease has relevance to the etiology and treatment of pulmonary and systemic hypertension. Recent discoveries have clarified how the anorexigens cause vasoconstriction and hypertension. Most anorexigens directly inhibit voltage-gated K+ (KV) channels in vascular smooth muscle cells (SMCs). This reduced K+ efflux leads to depolarization, the opening of voltage-sensitive Ca2+ channels, an increase in intracellular Ca2+ and vasoconstriction. Endothelial dysfunction appears to be a predisposing factor for the development of anorectic-induced vascular complications. Vasoconstriction is weak at clinically relevant doses of anorectic drugs. However, when nitric oxide synthase is inhibited, vasoconstriction is significantly enhanced. Anorexigens are the only drugs in widespread clinical use that have KV-channel-blocking properties and it is probable that much of their cardiovascular toxicity relates to this mechanism. Investigators need to examine new anorexigens and other therapeutic molecules for inhibitory effects on KV channels, as this effect may be a marker of drugs that will elicit vascular complications.
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PMID:Anorectic drugs and vascular disease: the role of voltage-gated K+ channels. 1237 23

A transient forebrain ischemia produced a delayed neuronal death of the hippocampus pyramidal cells in stroke-prone spontaneously hypertensive rats (SHRSP). Long term exposure of rats to stress has been reported to induce deleterious effects on the brain including morphological neuronal degeneration in the hippocampus. The present study was designed to examine the effects of psychological and physical stress on the ischemia-related neuronal death and the effects of 5-hydroxytryptamine(4) (5-HT(4)) receptor antagonist. SHRSP were exposed to the psychological or physical stress for 60 min in the communication box once or repeatedly for 3 days and occluded. SB204070, a 5-HT(4) receptor antagonist was injected before the occlusion. Seven days after the occlusion, the number of the neurons damaged morphologically was examined. A transient bilateral carotid occlusion produced a neuronal death of the CA1 subfield of the hippocampus in a time-dependent manner between 3 and 10 min. A 4 min occlusion induced very little morphological damage and a 5 min one produced a significant neuronal death. Exposure of rats to the psychological stress during 60 min for 3 days before the ischemic insults damaged the pyramidal cells by 4 min ischemia much more than without stress. Physical stress daily for 3 times also increased the damaged neurons. Pretreatment of SB204070 0.1 mg/kg after the stress exposure for 3 days significantly decreased the neuronal damage exacerbated by the stress exposure; however, it did not alter the damage induced by 4 or 10 min occlusion without stress. These results suggest that the repeated exposure of animals to the stress dramatically exacerbates the neuronal death by a transient ischemia and the 5-HT(4) receptor may be involved in the stress-induced exacerbating mechanism of the neuronal damage.
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PMID:Involvement of 5-hydroxytryptamine4 receptor in the exacerbation of neuronal loss by psychological stress in the hippocampus of SHRSP with a transient ischemia. 1272 57

The aim of the present study was to compare in man the innervation pattern and the functional responses to neuronal messengers in medium sized lenticulostriate and branches of the posterior cerebral arteries (PCA). The majority of the nerve fibers found were sympathetic and displayed specific immunoreactivity for tyrosine hydroxylase (TH) and neuropeptide Y (NPY). Only few nerve fibers displayed vasoactive intestinal polypeptide (VIP), calcitonin gene-related peptide (CGRP) and substance P (SP) immunoreactivity. In both arteries, the contractions induced by noradrenaline (NA), NPY and 5-hydroxytryptamine (5-HT) and the relaxant responses induced by acetylcholine (ACh), VIP and pituitary adenylate cyclase activating peptide-27 (PACAP) as well as CGRP and SP were compared in vitro. In conclusion, there was no major difference in innervation pattern or vasomotor sensitivity (pEC50 and pIC50 values) between the two vessels. However, the general pattern indicates stronger vasomotor responses (Emax and Imax) in the PCA branches as compared to the lenticulostriate arteries which may lend support for the clinical observation of a difference in stroke expression between the two vascular areas.
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PMID:Peptidergic and non-peptidergic innervation and vasomotor responses of human lenticulostriate and posterior cerebral arteries. 1557 98

Receptors have a prominent role in brain function, as they are the effector sites of neurotransmission at the postsynaptic membrane, have a regulatory role on presynaptic sites for transmitter reuptake and feedback, and are modulating various functions on the cell membrane. Distribution, density, and activity of receptors in the brain can be visualized by radioligands labeled for SPECT and PET, and the receptor binding can be quantified by appropriate tracer kinetic models, which can be modified and simplified for particular application. Selective radioligands are available for the various transmitter systems, by which the distribution of these receptors in the normal brain and changes in receptor binding during various physiologic activities or resulting from pathologic conditions can be visualized. The quantitative imaging for several receptors has gained clinical importance-for example, dopamine (D2)) receptors for differential diagnosis of movement disorders and for assessment of receptor occupancy by neuroleptics drugs; serotonin (5-hydroxytryptamine, 5-HT) receptors and the 5-HT transporter in affective disorders and for assessment of activity of antidepressants; nicotinic receptors and acetylcholinesterase as markers of cognitive and memory impairment; central benzodiazepine-binding sites at the gamma-aminobutyric acid A (GABAA) receptor complex as markers of neuronal integrity in neurodegenerative disorders, epilepsy, and stroke and as the site of action of benzodiazepines; peripheral benzodiazepine receptors as indicators of inflammatory changes; opioid receptors detecting increased cortical excitability in focal epilepsy but also affected in perception of and emotional response to pain; and several receptor systems affected in drug abuse and craving. Further studies of the various transmitter/receptor systems and their balance and infraction will improve our understanding of complex brain functions and will provide more insight into the pathophysiology of neurologic and psychiatric disease interaction.
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PMID:Brain receptor imaging. 1645 37

Antiplatelet agents such as sarpogrelate (SAR), a 5-hydroxytryptamine antagonist, and cilostazol (CIL), a phosphodiesterase-III inhibitor, are used in the management of peripheral vascular disease. In this study, we tested the hypothesis that both SAR and CIL prevent cardiac remodeling and improve cardiac function in congestive heart failure (CHF) due to myocardial infarction (MI). Post-MI rats (3 weeks after the occlusion of coronary artery) received either vehicle (MI+V, n = 36), SAR (MI+SAR; 5 mg xc kg(-1) x day(-1), n = 35) or CIL (MI+CIL; 5 mg x kg(-1) x day(-1), n = 34) from day 21 to day 56. Sham-operated rats (n = 29) served as controls. Electrocardiographic, echocardiographic, and hemodynamic parameters were measured on day 56. Treatment of infarcted animals with SAR or CIL significantly improved the left ventricular (LV) dimensions, LV fractional shortening, cardiac output, stroke volume, mean arterial pressure, LV diastolic function, and LV systolic pressure, as well as rates of LV pressure development and pressure decay. Although cardiac hypertrophy was reduced, both SAR and CIL had no effect on infarct size or MI-associated QTc prolongation. However, SAR decreased whereas CIL increased the incidence of ventricular arrhythmias and the mean number of episodes in infarcted animals. Mortality during the treatment period was decreased by 17% with SAR and increased by 10% with CIL, but these changes were not significant statistically. The data in this study suggest that both SAR and CIL prevent cardiac remodeling and improve cardiac function in MI-induced CHF; however, CIL unlike SAR increased the incidence of arrhythmias and adversely affected patient mortality.
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PMID:Antiplatelet therapy mitigates cardiac remodeling and dysfunction in congestive heart failure due to myocardial infarction. 1841 27


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